Journal Article Ahead of print
PubMed: 41801106 DOI: 10.1039/d5fo04465k
Beyond A1 milk concerns: dietary-relevant concentrations of β-casomorphin-7 show limited absorption but retain opioid-like activity in an intestinal cell model.
Food Funct
Authors: Giorgia Antonelli, Giovanni Piccinini, Mattia Santoni, Terenzio Bertuzzi, Davide Risso, Federico Canzoneri, Roberto Menta, Nicole Tosi, Liliana Milani, Cristian Del Bo', Alessandra Bordoni, Margherita Dall'Asta, Francesca Danesi
Affiliations
- Department of Agricultural and Food Sciences (DISTAL), University of Bologna, Piazza Goidanich 60, 47521 Cesena, Italy.
- Department of Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
- Department of Animal Science, Food and Nutrition, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy.
- Soremartec Italia Srl, Ferrero Group, Piazzale Ferrero 1, 12051 Alba, Italy.
- Department of Food and Drugs, University of Parma, Via Volturno 39, 43125 Parma, Italy.
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Celoria 2, 20133 Milan, Italy.
- Interdepartmental Centre for Industrial Agri-Food Research (CIRI-AGRO), University of Bologna, Via Quinto Bucci 336, 47521 Cesena, Italy.
Abstract
Milk and dairy products are a significant source of bioactive peptides, including β-casomorphin-7 (BCM-7), a heptapeptide released from the enzymatic cleavage of the A1 variant of β-casein. While some studies have suggested that BCM-7 may have detrimental effects on gastrointestinal physiology, the European Food Safety Authority found no established cause-and-effect relationship between the oral intake of BCM-7 and non-communicable diseases. This study aimed to investigate the biological effects of BCM-7 at physiologically relevant concentrations, corresponding to the estimated exposure levels in the European population, on the mucus-producing HT29-MTX-E12 intestinal cell line. Cells were treated with BCM-7 concentrations ranging from 4 to 120 µM for 4 hours, and various endpoints were assessed, including cytotoxicity, mucus production and secretion, opioid activity, inflammation, and peptide translocation across the intestinal barrier. BCM-7 treatment did not significantly affect cell viability, metabolic activity, or membrane integrity, except for a slight increase in LDH release at the highest concentration tested. No changes in mucin gene transcription levels (MUC5AC, MUC2) or mucus secretion were observed. However, BCM-7 treatment increased the expression of the µ-opioid receptor compared to the untreated control, confirming its opioid-like properties. While the IL-8 gene mRNA level increased at 120 µM, protein secretion remained unchanged, suggesting limited inflammatory effect. BCM-7 translocation across the intestinal barrier was minimal and inversely concentration-dependent, with most peptides likely degraded by dipeptidyl peptidase-4. These findings demonstrate that physiologically relevant BCM-7 concentrations exhibit opioid-like properties but have limited impact on mucus production, inflammation, and translocation of the intact peptide across the epithelial barrier in this in vitro intestinal model. The results provide mechanistic insights into BCM-7 effects while highlighting the need for further research considering individual dietary patterns and complex milk component interactions.
MeSH
Cells, Genes, Milk, Food, Therapeutics, Absorption